Abstract
Epidermal growth factor receptor (EGFR) is known to be critically involved in tissue development and homeostasis as well as in the pathogenesis of cancer. Here we showed that Foxp3(+) regulatory T (Treg) cells express EGFR under inflammatory conditions. Stimulation with the EGF-like growth factor Amphiregulin (AREG) markedly enhanced Treg cell function in vitro, and in a colitis and tumor vaccination model we showed that AREG was critical for efficient Treg cell function in vivo. In addition, mast cell-derived AREG fully restored optimal Treg cell function. These findings reveal EGFR as a component in the regulation of local immune responses and establish a link between mast cells and Treg cells. Targeting of this immune regulatory mechanism may contribute to the therapeutic successes of EGFR-targeting treatments in cancer patients.
Copyright © 2013 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amphiregulin
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Animals
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Antibodies, Neutralizing / pharmacology
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Cell Communication / immunology
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Colitis / chemically induced
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Colitis / immunology
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Colitis / metabolism
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Colitis / pathology
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EGF Family of Proteins
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ErbB Receptors / genetics
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ErbB Receptors / immunology*
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / immunology
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Gene Expression Regulation / drug effects
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Glycoproteins / antagonists & inhibitors
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Glycoproteins / genetics
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Glycoproteins / immunology*
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Glycoproteins / pharmacology
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Homeodomain Proteins / genetics
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Homeodomain Proteins / immunology
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Humans
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / immunology*
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Intercellular Signaling Peptides and Proteins / pharmacology
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Lymphocyte Activation / drug effects
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Mast Cells / drug effects
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Mast Cells / immunology
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Mast Cells / metabolism
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Melanoma, Experimental / genetics
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Melanoma, Experimental / immunology
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Melanoma, Experimental / pathology
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Membrane Proteins / administration & dosage
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Membrane Proteins / immunology
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Mice
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Mice, Transgenic
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Peptide Fragments / administration & dosage
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Peptide Fragments / immunology
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Signal Transduction / drug effects
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Signal Transduction / immunology
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T-Lymphocytes, Regulatory / drug effects
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / metabolism
Substances
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AREG protein, human
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Amphiregulin
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Antibodies, Neutralizing
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Areg protein, mouse
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EGF Family of Proteins
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Glycoproteins
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Homeodomain Proteins
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Intercellular Signaling Peptides and Proteins
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Membrane Proteins
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Peptide Fragments
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peptide SVYDFFVWL
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RAG-1 protein
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EGFR protein, mouse
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ErbB Receptors